Diabetic Distal Polyneuropathy Research Articles

Dynamics of Sensory and Motor Deficiency against the Background of Transcutaneous Electro Neuro Stimulation in the Therapy of Patients with Diabetic Distal Polyneuropathy

Dynamics of Sensory and Motor Deficiency against the Background of Transcutaneous Electro Neuro Stimulation in the Therapy of Patients with Diabetic Distal Polyneuropathy

A familial case of insulin-dependent diabetes mellitus with a mutation in the PTF1A gene

Diabetes mellitus (DM) is a genetically heterogeneous disease, and some cases of type 1 diabetes mellitus (T1DM) are caused by a mutation of one gene. The child has suffered from brittle diabetes since the age of 1 year and received insulin. The HbA1c level is 9.9—11.4%. The patient was examined at the age of 14 years; the disease duration is 13 years. The daily dose of insulin is 1.15—1.35 U/kg. DM complications include initial manifestations of distal diabetic polyneuropathy as well as cheiropathy. The mother (39 years) and grandmother (74 years) have T1DM with multiple complications. A genetic study revealed that all three family members had a heterozygous substitution p.P274 in the PTF1A gene with an unknown pathological significance.
 At present, it can not be asserted that the identified mutation is the etiologic factor of diabetes in the described case. We can not exclude T1DM in this child because specific antibodies have not been tested. However, the mutation is detected in all three members of the same family with diabetes, which does not exclude the discovery of a new form of MODY, not described earlier.

Restless legs syndrome in patients with distal diabetic polyneuropathy

Introduction/Objective. An association between restless legs syndrome (RLS) and etiologically different polyneuropathies is well established. However, the investigations about the prevalence of RLS in diabetic polyneuropathy (DP) have led to controversy. Our study objective was to determine the frequency of RLS in patients with distal symmetrical polyneuropathy in patients with diabetes and identify possible risk factors for its occurrence in this group of patients. Method. We investigated 101 consecutive patients with distal DP. RLS was diagnosed according to the International RLS Study Group diagnostic criteria. The distal symmetrical polyneuropathy was confirmed by the electromyoneurographic study performed in each patient. Results. Overall RLS was present in 27 (26.73%) patients. The comparison between patients with and without RLS revealed that the RLS+ group included more women than men (14.85/9.90% vs. 35.64/37.62%, non-significant), patients were significantly younger (60.58 ? 10.54 vs. 65.57 ? 10.94 years, p ? 0.05), sensory polyneuropathy was significantly more common (17/27 vs. 34/74, p ? 0.05); the average level of the total serum calcium concentration was higher in the RLS + group than in non-RLS (2.43 ? 0.26 vs. 2.28 ? 0.39; p ? 0.05). However, multivariate logistic regression analysis did not demonstrate these as significant independent risk factors for RLS in DP. Conclusions. RLS is common in DP and occurs in more than a quarter of these patients. Though sensory forms and higher total serum calcium concentration were associated with RLS, neither of these has been identified as a significant single risk factor for the development of RLS in DP.

NaV channel variants in patients with painful and nonpainful peripheral neuropathy.

Objective:To examine the incidence of nonsynonymous missense variants in SCN9A (NaV1.7), SCN10A (NaV1.8), and SCN11A (NaV1.9) in patients with painful and nonpainful peripheral neuropathy.Methods:Next-generation sequencing was performed on 457 patient DNA samples provided by the Peripheral Neuropathy Research Registry (PNRR). The patient diagnosis was as follows: 278 idiopathic peripheral neuropathy (67% painful and 33% nonpainful) and 179 diabetic distal polyneuropathy (77% painful and 23% nonpainful).Results:We identified 36 (SCN9A), 31 (SCN10A), and 15 (SCN11A) nonsynonymous missense variants, with 47.7% of patients carrying a low-frequency (minor allele frequency <5%) missense variant in at least 1 gene. The incidence of previously reported gain-of-function missense variants was low (≤3%), and these were detected in patients with and without pain. There were no significant differences in missense variant allele frequencies of any gene, or SCN9A haplotype frequencies, between PNRR patients with painful or nonpainful peripheral neuropathy. PNRR patient SCN9A and SCN11A missense variant allele frequencies were not significantly different from the Exome Variant Server, European American (EVS-EA) reference population. For SCN10A, there was a significant increase in the alternate allele frequency of the common variant p.V1073A and low-frequency variant pS509P in PNRR patients compared with EVS-EA and the 1000 Genomes European reference populations.Conclusions:These results suggest that identification of a genetically defined subpopulation for testing of NaV1.7 inhibitors in patients with peripheral neuropathy is unlikely and that additional factors, beyond expression of previously reported disease “mutations,” are more important for the development of painful neuropathy than previously discussed.

TREATMENT OF DIABETIC DISTAL POLYNEUROPATHY WITH ACTOVEGIN® IN TYPE 2 DIABETIC PATIENTS.

The possibilities of treatment of diabetic polyneuropathy with Actovegin® are discussed in this publication. In the multicenter, randomized, double-blind trial 567 patients with type 2 diabetes received 20 intravenous infusions of 20% solution of Actovegin® or placebo followed by 1800 mg of Actovegin® in tablets or placebo for 140 days. The effectiveness was assessed by changes of Total Symptom Score and vibration perception as primary outcomes, neuropathy impaired score of the lower limbs (NIS-LL) and quality of life as secondary end points. Treatment with Actovegin resulted in significant improvement in TSS (p = 0,0003), sensory component of NIS-LL (p = 0,021), improvement of vibration perception (р = 0,08) and mental domain of quality of life. Thus, treatment of diabetic distal polyneuropathy with Actovegin® in type 2 diabetic patients improves different functions of peripheral nervs.

Evaluation of vibration sensitivity violation as early diagnosis of diabetic distal polyneuropathy in patients with type 2 diabetes

Distal sensorimotor polyneuropathy (DSPN) is a severe complication and the most common form of peripheral neuropathies in patients with type 2 diabetes (T2D). Nowadays, interest in the DSPN has increased significantly due to the increase of incidence of T2D, as well as the severity of its clinical manifestations.This study aimed to assess the prevalence of DSPN in patients with T2D using Vibratip device as an alternative test for early diagnosis of vibration perception disorders.Design and methods. This study was a cross sectional observational design. Height, weight, body mass index (BMI), systolic and diastolic blood pressure measured according to standard protocol. The information about T2D duration and treatment, diabetic complications, concomitant diseases and its treatment, data about laboratory parameters (level of HbA1c during the last six months, total cholesterol and triglycerides) collected from local database. All participants examined with Vibratip on both feet. Vibratip is new device using standardized vibration for DSPN detection. Vibratip is applied to the patients feet, testing two sites on both feet (1st metatarsal head on the plantar surface and hallux pump) - once whilst non-vibrating and once whilst vibrating and the patients (with their eyes closed) is asked to indicate when they feel the vibration.Results. 2757 women and 1546 men aged 22-89 years selected from the six regions of the Republic of Belarus and Minsk-city. Among the 4303 subjects 7.78% (n=335) took place in this study aged less than 45 years (young patients), 65.4 % (n=2814) aged 45-65 years and 26.49 % (n=1140) aged more than 65 years old. Average age was 59 ±10.4; average body mass index (BMI) – 32.2±5.6 kg/m2. Participants with normal body mass index composed 9.02% (n=388), participants with superfluous body mass and obesity – 91% (n=3915). 710 (16.5%) participants were smoking, 2649 (61 %) suffered from high blood pressure. The most participants 1428 (33%) were treated by statins compared with fibrates 131 (3%). In patients with clinical symptoms of DSPN more often was pain (in 775 cases - 18.0%), burning (in 775 cases - 16.4%), numbness (in 1144 cases - 26.6%), feeling of pins and needles (in 921cases - 21.4%) and feeling of electric shock (in 235 cases - 5.5%). In patients with vibration sensitivity disorders were subjects with previous diagnosis of DSPN 1813 (42.13%) and subjects without previous diagnosis of DSPN 850 (19.75%). Amount subjects with asymptomatic vibration sensitivity disorder without clinical symptoms DSPN was 1640 (38.12%).Conclusions. In 20% of patients T2D with impaired vibration sensitivity, established with the device Vibratip, defined pre-clinical stage of DSPN. Given the ease of use of the device Vibratip advisable its use as a screening method for early diagnosis of DSPN in clinical practice.

Neurologic diseases that cause female urinary retention

Objective: The pathogenesis of female urinary retention is not well known. Hence, we systematically investigated the frequency of diseases that underlie female urinary retention in a urodynamic laboratory.Methods: We analyzed data from 450 consecutive female patients. Data registries included the diagnosis, lower urinary tract symptom questionnaires, urodynamic study results, and neurologic exam observations. Complete urinary retention is defined as mean post-void residual (PVR) urine volume &gt; 100 ml with no voluntary void at all; whereas incomplete urinary retention is defined as mean PVR urine volume &gt; 100 ml after voluntary partial void.Results: Sixty of the 450 female patients visiting our lab (13%) had urinary retention with 4 (6.7%) of these having complete retention and 56 (93.3%) having incomplete retention. The most common underlying disease in these 60 patients was lumbar spondylosis (LS), 38.3% (with 16 patients having LS alone and 7 having LS &amp; diabetic distal polyneuropathy [DPN]), multiple system atrophy (MSA), 18.3%, and DPN, 14.4% (with 2 patients having DPN alone and 7 having LS &amp; DPN), followed by drug-induced retention (e.g., by antidepressants), 8.3%, acute myelitis of possible demyelinating origin, 5.0%, and other etiologies. An underactive detrusor was the major urodynamic findings in those patients.Conclusion: The present study revealed that common etiologies for female urinary retention are neurologic, e.g., an underactive detrusor due to MSA, age-related LS, and lifestyle-related DPN. Therefore LS and DPN, both common diseases, should also become major treatment targets in order to maximize patients’ quality of life.

ELECTRONEUROMYOGRAPHY IN DIAGNOSTICS OF EARLY STAGES OF DIABETIC NEUROPATHY – INVITATION OF ENDOCRINOLOGISTS, NEUROLOGISTS AND ELETCROPHYSIOLOGISTS TO DISCUSSION

The urgency of the problem of diabetic distal polyneuropathy (DDPN) is preconditioned by its great prevalence, according to specialized studies data, late diagnostics and serious consequences. The importance of DDPN diagnostics at its early stage doesn’t generate doubts: just at this period disturbance of peripheral nerves is of reciprocal nature and the therapy is effective to the maximum degree. But the objectification of the DDPN diagnosis is difficult: the data of neurologic and electrophysiological tests often do not correspond to the clinical symptoms and signs as these methods evaluate lesions of large nervous fibers whereas in DDPN it’s small fibers that are damaged in the first place. Use of skin biopsy and confocal corneal microscopy for evaluation of small fibers is extremely restricted in a clinical practice. Possibilities of electroneuromyography (ENMG) are analyzed as an option: parameters with their subjective peculiarities, selection of nerves and their number for DDPN diagnostics as a context of topographic neurology and neurophysiology of distal fibers.

Clinical diagnosis of distal diabetic polyneuropathy using neurological examination scores: correlation with nerve conduction studies

The aim of this study was to diagnose diabetic sensorimotor polyneuropathy using neurological examination scores and to correlate the findings with nerve conduction studies (NCS). Thirty patients with type 2 diabetes were included in the study. Detection and grading of neuropathy were carried out based on the Diabetic Neuropathy Symptom (DNS) Score, modified Neuropathy Symptom Score (NSS), Diabetic Neuropathy Examination (DNE), and modified Neuropathy Disability Score (NDS). For the NCS, amplitudes, velocities, and latencies of seven nerves — that is, four motor (median, ulnar, tibial, and common peroneal) and three sensory (median, ulnar, and sural) nerves — were recorded. If the patient had two or more abnormal findings in any of these nerves, the patient was diagnosed as having peripheral sensorimotor neuropathy. Thereafter, the sensitivity, specificity, and diagnostic efficacy of each neurological score were recorded taking NCS as the gold standard. Diabetic sensorimotor polyneuropathy was diagnosed clinically and electrophysiologically in 17 patients (56.7%). However, there were nine cases (30%) of subclinical neuropathy. Neurological examination scores were significantly correlated with each other and with individual variables of NCS and the nerve conduction sum score. Taking the NCS as gold standard, DNS, modified NSS, DNE, and modified NDS had 65.4, 61.5, 30.8, and 61.5% sensitivity and 100, 75, 100, and 100% specificity, respectively. Their diagnostic efficacies were 70, 63.3, 40, and 66.7%, respectively. Neurological examination scores can detect and grade neuropathy in the majority of cases. However, NCS was accurate for detection of diabetic sensorimotor polyneuropathy, especially for the subclinical neuropathies.

EFFICACY OF ACTOVEGIN IN THE TREATMENT OF THE CENTRAL AND THE PERIPHERAL NERVOUS SYSTEM

The stimulator of tissue regeneration Actovegin is used in many diseases associated with blood circulation. It’s given to patients with neurological, endocrinological, cardiac and even ophthalmic diseases. Its efficacy is observed in disorders of the brain with the metabolic and vascular nature. It improves the trophism of tissues with injuries, burns and ulcers of the different etiology. It prevents the development of adverse effects as a result of peripheral vascular disorders. Actovegin has received the active application in patients with the long-standing diabetes as a prevention and the treatment of complications, particularly the vascular dementia and the diabetic distal polyneuropathy. The basis for these diseases is the hypoxic nature of the tissue damage. It’s mechanisms direct to the reduction of the influence pathological factors and the recovery of the antioxidant activity of cells.

Association study of C936T polymorphism of the VEGF gene and the C242T polymorphism of the p22phox gene with diabetes mellitus type 2 and distal diabetic polyneuropathy.

Even with long‑term glycemic control, diabetes mellitus type 2 (DM2) remains the predominant cause of diabetic neuropathy. Single nucleotide polymorphism (SNP) C936T of the vascular endothelial growth factor (VEGF) gene and the SNP C242T of the p22phox (CYBA) gene have been investigated in relation to DM2 and its complications. The aim of the present study was to investigate the association between these two SNPs and DM2, and also between the SNPs and the signs and symptoms of diabetic distal polyneuropathy. The DM2 group consisted of 98 individuals and the control group consisted of 104 individuals. The results demonstrated that there was no association between the different genotypes or alleles and increased risk of the disease (P>0.05). With SNP C242T, a significant association with body mass index between the CTxTT genotypes (P=0.043) was identified; and the greatest body mass indexes were among individuals with the TT genotype. An association between the degree of neuropathic symptoms and genotypic/allelic distribution of these polymorphisms was not observed. In conclusion, the investigated polymorphisms are not correlated with the risk of developing DM2.

Evaluation of violation vibration sensitivity for early diagnosis of diabetic distal polyneuropathy in patients with type 1 diabetes in the Republic of Belarus

Evaluation of violation vibration sensitivity for early diagnosis of diabetic distal polyneuropathy in patients with type 1 diabetes in the Republic of Belarus

Clinical and functional status of the peripheral nervous system in patients with diabetic polyneuropathy

It seems impossible at the moment to stem the incidence of diabetes despite the enormous efforts to address this global problem. We have examined 30 patients with type 2 diabetes to study the clinical and functional status of the peripheral nervous system in patients with diabetic distal polyneuropathy. Our works showed the importance of both clinical and electroneuroneuromiographic examination of patients with diabetes who have or do not have objective manifestations of polyneuropathy. This allows for early detection of the initial effects of polyneuropathy. In patients with symptomatic stage of diabetic polyneuropathy, this method allows to establish the pattern, nature, and severity of lesions of fibers of peripheral nerve trunks.

The clinical and functional state of peripheral nervous system during the treatment of patients with diabetic polyneuropathy

The state of the peripheral nervous system and treat- ment of patients with diabetic polyneuropathy is global problem. To study the clinical and functional status of the peripheral nervous system in patients with diabetic distal polyneuropathy we have examined 30 patients with type 2 diabetes. Our research showed the importance of both clinical and electroneuromyographic examination for patients with diabetes who may have or do not to have objective evidence of polyneuropathy. This allows for early detection of initial effects of polyneuropathy and improve treatment tactics.

Применение транскожной электронейростимуляции в комплексном восстановительном лечении диабетической полинейропатической боли

. In this article expediency of application of monophasic, high frequency and low amplitude transcutaneous neuroelectrostimulation in treatment of neuropathic pain in patients with diabetic distal polyneuropathy of lower extremity was proved.&#x0D; This study included 159 patients with acute distal neuropathic pain in lower extremity. In all patients di-abetic mellitus 2 type was diagnosed and clinical signs and symptoms of distal polyneuropathy were found.&#x0D; Comparative dynamics of clinical and electromyographic manifestations of diabetic distal polyneuropathy between basis and control groups were analyzed. 62 patients in control group undergone treatment by the Duloxetine 60 mg every day within 3 months. In basis group 97 patients in addition to the Duloxetine were treated by transcutaneous neuroelectrostimulation during 30 minutes per day after day for 15 days.&#x0D; This study showed that complex treatment by combination use of transcutaneous neuroelectrostimula-tion with central analgesic more effective than traditional analgesic therapy in treatment of neuropathic pain in patients with diabetic distal polyneuropathy.&#x0D;

Aging and pain: specific features of neuropathy treatment in the elderly

The changes in the somatosensory system in aging and peripheral neuropathies are similar. Higher pain sensitivity thresholds in the presence of axonopathy are accompanied by paradoxically decreased pain tolerance associated with neuroplastic changes in the spinal cord and brain. The symptomatic treatment of neuropathic pain syndrome with antidepressants, anticonvulsants, and opioids is related to the lower quality of life in elderly patients and to the high risk of severe side effects. The pathogenetic treatment of polyneuropathies frequently increases the intensity of neuropathic pain at its beginning; however, it can recover the function of an axon and reduce the degree of deficiency states. The paper discusses methods for increasing the safety of treatment for neuropathic pain in elderly patients, a relationship between the pathogenesis of nervous system aging and distal diabetic polyneuropathy, and ways of their correction.

Urinary Methylmalonic Acid as an Indicator of Early Vitamin B12 Deficiency and Its Role in Polyneuropathy in Type 2 Diabetes

The rising incidence of diabetes and its negative impact on quality of life highlights the urgent need to develop biomarkers of early nerve damage. Measurement of total vitamin B12 has some limitations. We want to determine the levels of urinary methylmalonic acid and its relationships with serum vitamin B12 and polyneuropathy. The 176 Chinese patients with Type 2 diabetes mellitus were divided into 3 groups according to the levels of vitamin B12. A gas chromatography mass spectrometric technique was used to determine blood methylmalonic acid and urinary methylmalonic acid. The diagnosis of distal diabetic polyneuropathy was based on the determination of bilateral limb sensory and motor nerve conduction velocity and amplitude with electromyogram. Multiple regression analysis revealed that urinary methylmalonic acid/creatinine, blood methylmalonic acid, and so forth were variables that influenced diabetic polyneuropathy significantly. Nerve sensory conduction velocity and nerve amplitude in the group of urinary methylmalonic acid/creatinine >3.5 mmol/mol decreased significantly. Superficial peroneal nerve sensory and motor conduction velocity and ulnar nerve compound motor active potential amplitude were inversely correlated with urinary methylmalonic acid/creatinine. Urinary methylmalonic acid correlates with serum vitamin B12 levels in person with diabetes and is a sensitive marker of early polyneuropathy.

The relationship between characteristics of calcinosis of the arteries of the lower extremities and the severity of distal neuropathy in the patients with diabetes mellitus

Aim. To estimate the degree of arterial calcinosis in the distal segments of the lower extremities in the patients presenting with diabetes mellitus (DM) and varying severity of distal diabetic polyneuropathy (DPN). Materials and methods. The study involved 61 patients with DM ( 21 men and 40 women, mean age 51.4 +- 11.68 years) of whom 27 suffered DM1 and 34 DM2. Group 1 was comprised of 37 patients with diabetic osteoarthropathy (DOAP), group 2 included 13 patients with severe DPN, and group 3 11 patients having moderate DPN. All the patients underwent comprehensive laboratory and instrumental examination including measurement of peripheral sensitivity and electromyography. The degree of arterial calcinosis in the distal segments of the lower extremities was determined using multispiral computed tomography (MSCT) with the calculation of the Agatston tibial artery calcification scores. Results. The groups were matched for the patients' age, duration of disease, total cholesterol and creatinin levels, and glomerular filtration rate. Moreover, the patients of groups 1 and 2 were matched for the functional state of nerve fibers in the lower extremities and were significantly different in respect to this characteristic from the patients of group 3. Median of the Agatston tibial artery calcification scores in group 1 was 365.4 (min - 0, max - 1600) and in group 2 2.7 (min - 0, max - 74.6). Groups 1 and 2 were comparable in terms of the degree of calcinosis and were significantly different from group 3 (p &lt; 0.05 1 vs 3; p &lt; 0.005 2 vs 3). The Agatston tibial artery calcification scores negatively correlated with the motor response (r = -0.3; p &lt; 0.05) and vibrational sensitivity (r = -0.4, p &lt; 0.01). Conclusion. Results of the study suggest the leading role of DPN in the development and progression of arterial calcinosis in the distal segments of the lower extremities in the patients with diabetes mellitus.

Role of distal diabetic polyneuropathy in the development of media calcification in patients with diabetesmellitus

Arterial media calcification is a common finding in diabetes mellitus (DM) and is associated with distal symmetric neuropathy. Arterialcalcification also emerges as a complication of chronic kidney disease and is considered to be a risk factor for cardiovascular andgeneral morbidity. "Calcification" is actually not an accurate term, because morphologic alterations also include bone tissue formationor "ossification". Both processes are complex and exist in tight connection with bone homeostasis. Connection between distal symmetricneuropathy and arterial calcification suggests that neuropathy may be an independent risk factor for cardiovascular morbidity.

Prevalence of distal diabetic polyneuropathy using quantitative sensory methods in a population with diabetes of more than 10 years’ disease duration

Results of studies on the prevalence of distal diabetic polyneuropathy (DPN) are contradictory. Conventional methods used for the diagnosis of DPN in clinical practice have limited effectiveness. The present study aimed to assess the prevalence of DPN in a population with long-standing diabetes (more than 10 years disease duration) by measuring vibratory, thermal and tactile sensitivities with quantitative sensory devices, as well as their relationship with associated clinical risk factors. A total of 1011 diabetic patients were evaluated in a multicenter, cross-sectional, observational study. The three sensitivities were assessed by ultrabiothesiometer, aesthesiometer and thermoskin devices, respectively. The prevalence of neuropathic pain was validated by the DN4 questionnaire. Of the 1011 cases included, 400 (39.6%) met the diagnostic criteria of DPN, while no DPN was found in the remaining 611 (60.4%). Of the 400 patients with DPN, 253 (63.2%) showed clinical manifestations, while 147 (36.8%) were diagnosed as subclinical DPN. The prevalence of DPN increased with disease duration. There was a progressive loss of the three sensitivities with increased disease duration, particularly thermal and vibratory sensitivities. This loss was statistically significant for the latter two sensitivities. Among patients with clinical DPN, 84.2% had painful neuropathic symptoms. The prevalence of DPN was positively related to micro- and macroangiopathic complications and with dyslipidemia. This study reveals a high degree of underdiagnosis of DPN, most likely due to the asymptomatic nature of the disease in a considerable proportion of patients. Our observations provide evidence of the usefulness of specific equipment for quantitative and objective assessment of polyneuropathy.